Possible potentiation of the abscopal effect of ionising radiation by modulated electro-hyperthermia in locally advanced cervical cancer patients

INTRODUCTION: Literature has shown that the local application of ionising radiation is able to induce a response at distant sites of disease. This effect, known as the abscopal effect, is generally accepted to be mediated by the triggering of an immune response by ionising radiation. The application of hyperthermia has also been suggested to enhance the abscopal effect. Our ongoing phase III, randomised clinical study investigates the effects of the addition of modulated electro-hyperthermia (mEHT) on chemoradiotherapy in locally advanced cervical patients. We assess the response of the tumour and lymph nodes inside and outside of the radiation treatment field based on PET/CT images and report on the potential abscopal effect mediated by mEHT. METHODS: Participants enrolled in the study had FIGO stage IIb (distal parametrium involvement) to IIIb (bilateral hydronephrosis excluded) cervical cancer. HIV positive participants were included if their CD4 count was >200cells/mL or they had been on antiretroviral therapy for more than 6 months. Participants were randomised into a mEHT arm or a control arm. All participants were prescribed 50Gy external beam radiation to the pelvis in 25 fractions, plus 3 fractions of 8Gy High Dose Rate (HDR) Brachytherapy. Participants in the mEHT arm were prescribed 2 mEHT treatments per week during external beam radiation using modulated 13.56MHz capacitive heating (55 minutes; 130W). 155 pre-treatment and 155 post-treatment 18F-FDG PET/CT scans were analysed. Each region (head and neck; thorax; abdomen; pelvis) was scored according to the nodes visualised on 18F-FDG PET/CT: no change in the number of visualised nodes; resolution of all nodes; new nodes; no nodes in either pre- or post-treatment scans. Tumour response was reported based on PERCIST version 1.0 criteria. RESULTS: 56% and 62% of the participants in the mEHT and control arm respectively had nodes with an 18F-FDG Standard Uptake Value of more than 2.5 visualised on PET/CT before treatment. A complete metabolic response of the tumour was significantly higher in the participants in the mEHT group than in the participants in the control group (58% versus 37% respectively). The number of participants with a complete metabolic response of the tumour and extra-pelvic nodes was also significantly higher in the mEHT group versus in the control group (27.7% vs 6.8%; Chi2: p=0.009). CONCLUSIONS: In our study, the addition of mEHT may be contributing to an enhanced abscopal effect with a significantly higher increase in the complete metabolic response of nodal disease outside of the treated area observed in the mEHT group